Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections

Zhang, Yue; Guo, Xiaonan; Guo, Mengze; Chen, Hong; Li, Bo; Yu, Jinfei; Gu, Tiejun; Kong, Wei; Wu, Yongge

doi:10.1007/s12026-019-09107-6

Cited by 11 publications

(7 citation statements)

References 49 publications

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“…Intranasal immunization can induce not only systemic specific but also specific local mucosal immune responses ( 38 , 39 ). However, compared with subcutaneous and intramuscular injection of antigens, intranasal vaccination is less efficient in inducing systemic immunity ( 40 , 41 ), which is consistent with the stronger serum IgG responses in the intramuscular vaccination (S1/IM and S1-BLPs/IM) groups than those in the intranasal vaccination (S1/IN and S1-BLPs/IN) groups in this study.…”

Section: Discussionsupporting

confidence: 84%

Intranasally inoculated bacterium-like particles displaying porcine epidemic diarrhea virus S1 protein induced intestinal mucosal immune response in mice

Su,

Wang,

Yuan

et al. 2023

Front. Immunol.

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Porcine epidemic diarrhea virus (PEDV) causes acute watery diarrhea and high mortality in newborn piglets. Activation of intestinal mucosal immunity is crucial to anti-PEDV infection. To develop a vaccine capable of stimulating intestinal mucosal immunity, we prepared a bacterium (Lactococcus lactis)-like particle (BLP) vaccine (S1-BLPs) displaying the S1 protein, a domain of PEDV spike protein (S), based on gram-positive enhancer matrix (GEM) particle display technology. We further compared the effects of different vaccination routes on mucosal immune responses in mice induced by S1-BLPs. The specific IgG titer in serum of intramuscularly immunized mice with S1-BLPs was significantly higher than that of the intranasally administered. The specific IgA antibody was found in the serum and intestinal lavage fluid of mice vaccinated intranasally, but not intramuscularly. Moreover, the intranasally inoculated S1-BLPs induced higher levels of IFN-γ and IL-4 in serum than the intramuscularly inoculated. In addition, the ratio of serum IgG2a/IgG1 of mice inoculated intramuscularly was significantly higher with S1-BLPs compared to that of with S1 protein, suggesting that the immune responses induced by S1-BLPs was characterized by helper T (Th) cell type 1 immunity. The results indicated that S1-BLPs induced systemic and local immunity, and the immunization routes significantly affected the specific antibody classes and Th immune response types. The intranasally administered S1-BLPs could effectively stimulate intestinal mucosal specific secretory IgA response. S1-BLPs have the potential to be developed as PEDV mucosal vaccine.

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Section: Discussionsupporting

confidence: 84%

Intranasally inoculated bacterium-like particles displaying porcine epidemic diarrhea virus S1 protein induced intestinal mucosal immune response in mice

Su,

Wang,

Yuan

et al. 2023

Front. Immunol.

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“…Future mucosal vaccines could benefit from heterologous prime-boosting approaches. While mucosal immunization would induce SIgA antibodies, parenteral doses would improve systemic response [48][49][50]. Data from rodents showed that nasal immunization enhanced IgA in sera [46] and both sera and respiratory mucosa [47].…”

Section: Secretory Iga: the Mucosal Weaponmentioning

confidence: 99%

Vaccines, adjuvants and key factors for mucosal immune response

Portilho

Gaspari

2022

Immunology

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Vaccines are the most effective tool to control infectious diseases, which provoke significant morbidity and mortality rates. Most vaccines are administered through the parenteral route and can elicit a robust systemic humoral response, but they induce a weak T-cell-mediated immunity and are poor inducers of mucosal protection. Considering that most pathogens enter the body through mucosal surfaces, a vaccine that elicits protection in the first site of contact between the host and the pathogen is promising. However, despite the advantages of mucosal vaccines as good options to confer protection on the mucosal surface, only a few mucosal vaccines are currently approved. In this review, we discuss the impact of vaccine administration in different mucosal surfaces; how appropriate adjuvants enhance the induction of protective mucosal immunity and other factors that can influence the mucosal immune response to vaccines.

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“…The limited coverage of the licensed vaccines, broad geographical variation in circulating serotypes, non-vaccine serotype replacement, and the prevalence of non-encapsulated pneumococci from patients with invasive pneumococcal disease (IPD) are key reasons for an attempt to overcome the pneumococcal vaccine limitations and design the novel serotype-independent vaccines [ 7 – 11 ]. Pneumococcal protein-based vaccine (PPV) formulation is a cost-effective and promising candidate for serotype-independent vaccine development [ 12 , 13 ]; and many pneumococcal conserved cell-surface proteins have already been identified as ideal antigens for PPV in recent years [ 6 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

Afshari

Cohan

Sotoodehnejadnematalahi

et al. 2023

J Transl Med

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Background The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family. Methods To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA1-5c+p vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA1-5c+p, we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA1-5c+p antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay. Results For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA1-5c+p protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA1-5c+p IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells. Conclusion Our findings elucidated the potential application of the PspA1-5c+p vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA1-5c+p vaccine candidate.

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Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections

Cited by 11 publications

References 49 publications

Intranasally inoculated bacterium-like particles displaying porcine epidemic diarrhea virus S1 protein induced intestinal mucosal immune response in mice

Intranasally inoculated bacterium-like particles displaying porcine epidemic diarrhea virus S1 protein induced intestinal mucosal immune response in mice

Vaccines, adjuvants and key factors for mucosal immune response

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

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